Postmenopausal hormone therapy taken at age 50-55 years produces no sustained benefit or harm to cognitive function, according to a report published online June 24 in JAMA Internal Medicine.
Women randomly assigned to receive a mean of 7 years of treatment with conjugated equine estrogens (CEEs) showed similar global cognitive function, as well as similar function in several individual cognitive domains, as those randomly assigned to receive placebo in the Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y).
A previous study of WHI participants who were at least 65 years old at enrollment showed that women given hormone therapy (HT) had small deficits in global and domain-specific cognitive functioning that persisted for years after treatment ended. Therefore, these findings concerning younger women "provide reassurance that CEE-based therapies, when administered to women earlier in the postmenopausal period, do not seem to convey long-term adverse consequences for cognitive function," said Mark A. Espeland, Ph.D., of the department of biostatistical sciences, Wake Forest University, Winston-Salem, N.C., and his associates.
Dr. Mark A. Espeland
However, these results also refute the "window of opportunity" hypothesis that HT might preserve or promote brain health when given just as ovarian function declines at the onset of menopause, rather than later in the process.
The WHIMS-Y study was an extension of the WHI in which 1,372 women agreed to participate in long-term follow-up after the WHI concluded. These women had been 50-55 years of age at enrollment in the WHI and had taken either HT or placebo for a mean of 7 years (range, 4-10 years) for that study.
For the WHIMS-Y study, they underwent cognitive assessment at a mean age of 68 years (range, 63-74 years).
The primary outcome was global cognitive function as measured by the Telephone Interview for Cognitive Status-modified (TICS-m). There was "essentially no difference" on this measure between women who had taken active HT and those who had taken placebo, after the data were adjusted for patient age.
In addition, no significant differences were found between the two study groups on measures of immediate and delayed verbal memory, attention, executive function, verbal fluency, and working memory, Dr. Espeland and his colleagues reported (JAMA Intern. Med. 2013 June 24 [doi: 10.1001/jamainternmed.2013.7727]).
These findings were consistent, regardless of whether the HT had been CEE alone or CEE in combination with medroxyprogesterone acetate.
Adjusting the data to account for risk factors for cognitive impairment did not alter the results. The findings also remained consistent across several subgroup analyses, with one exception: Women who had taken and then stopped HT before enrollment in the WHI and who had then resumed HT as part of the WHI showed a deficit in verbal fluency. However, this might have been a chance finding, the researchers noted.
"Although we cannot rule out acute benefits or harm, these do not appear to be present to any degree a mean of 7 years after cessation of [HT]," they said.
This study was supported by the National Institute on Aging; the WHI was funded by the National Heart, Lung, and Blood Institute. Dr. Espeland had no disclosures. One of his associates reported ties to several companies, including Amarin, Amgen, and Daiichi-Sankyo.